216 research outputs found
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Development of a new radiolabel (lead-203) and new chelating agents for labeling monoclonal anntibodies for imaging
High liver uptake and slow body clearance presently limit the usefulness of /sup 111/In labeled antibodies for tumor imaging. We have investigated /sup 203/Pb as an alternate and better antibody label. The DTPA and cyclohexyl EDTA (CDTA) conjugates of an anticolon carcinoma antibody, 17-1A were labeled (bicyclic anhydride method) with /sup 203/Pb and /sup 111/In with 60 and 90% labeling yields, respectively. The biodistribution of /sup 203/Pb-17-1A conjugates was compared with the corresponding /sup 111/In-labeled preparations and with /sup 203/Pb-DTPA, /sup 203/Pb-nitrate and nonrelevant antibody controls in normal and human tumor (SW948) xenografted nude mice at 24, and 96 hr. Lead-203-labeled CDTA and DTPA antibody conjugates gave similar in vivo distributions. Even though the lead bound to these chelate-antibody conjugates was more labile in serum and in vivo, compared to indium, it cleared much faster from the liver and the whole body. A new series of chelating agents based on the incorporation of a trans-1,2- diaminocyclohexane moiety into the carbon backbone of polyaminocarboxylates is being synthesized. These are expected to provide stronger complexing ability for lead and produce greater in vivo stability. These ligands are also expected to be superior to EDTA and DTPA for labeling antibodies with other radiometals, including indium. 32 refs., 3 tabs
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Development and evaluation of copper-67 and samarium-153 labeled conjugates for tumor radioimmunotherapy
The potential of utilizing receptor-specific agents such as monoclonal antibodies (MAb), and MAb-derived smaller molecules, as carriers of radionuclides for the selective destruction of tumors has stimulated much research activity. The success of such applications depends on many factors, especially the tumor binding properties of the antibody reagent, the efficiency of labeling and in-vivo stability of the radioconjugate and, on the careful choice of the radionuclide best suited to treat the tumor under consideration. The radiolabeled antibody technique for radioimmunotherapy (RIT), however, has experienced many limitations, and its success has not matched the expectations that were raised more than a decade ago. The problems that have been identified include: (i) degradation of antibody immunoreactivity resulting from chemical manipulations required for labeling; (ii) lack of suitable radioisotopes and methods for stable attachment of the radiolabel; (iii) in-vivo instability of the radioimmunoconjugates; (iv) excessive accumulation of activity in non-target locations; and (v) lack of radioimmunoconjugate accessibility to cells internal to a tumor mass. A careful choice of the radionuclide(s) best suited to treat the tumor under consideration is one of the most important requirements for successful radioimmunotherapy. This study evaluates copper 67 and samarium 153 for tumor radioimmunotherapy
Localisation of NMU1R and NMU2R in human and rat central nervous system and effects of neuromedin-U following central administration in rats
Rationale: Neuromedin-U (NmU) is an agonist at NMU1R and NMU2R. The brain distribution of NmU and its receptors, in particular NMU2R, suggests widespread central roles for NmU. In agreement, centrally administered NmU affects feeding behaviour, energy expenditure and pituitary output. Further central nervous system (CNS) roles for NmU warrant investigation.
Objectives: To investigate the CNS role of NmU by mapping NMU1R and NMU2R mRNA and measuring the behavioural, endocrine, neurochemical and c-fos response to intracerebroventricular (i.c.v.) NmU. Methods: Binding affinity and functional potency of rat NmU was determined at human NMU1R and NMU2R. Expression of NMU1R and NMU2R mRNA in rat and human tissue was determined using semi-quantitative reverse-transcription polymerase chain reaction. In in-vivo studies, NmU was administered i.c.v. to male Sprague-Dawley rats, and changes in grooming, motor activity and pre-pulse inhibition (PPI) were assessed. In further studies, plasma endocrine hormones, [DOPAC + HVA]/[dopamine] and [5-HIAA]/[5-HT] ratios and levels of Fos-like immunoreactivity (FLI) were measured 20 min post-NmU (i.c.v.).
Results: NmU bound to NMU1R (KI, 0.11±0.02 nM) and NMU2R (KI, 0.21±0.05 nM) with equal affinity and was equally active at NMU1R (EC50, 1.25±0.05 nM) and NMU2R (EC50, 1.10±0.20 nM) in a functional assay. NMU2R mRNA expression was found at the highest levels in the CNS regions of both rat and human tissues. NMU1R mRNA expression was restricted to the periphery of both species with the exception of the rat amygdala. NmU caused a marked increase in grooming and motor activity but did not affect PPI. Further, NmU decreased plasma prolactin but did not affect levels of corticosterone, luteinising hormone or thyroid stimulating hormone. NmU elevated levels of 5-HT in the frontal cortex and hypothalamus, with decreased levels of its metabolites in the hippocampus and hypothalamus, but did not affect dopamine function. NmU markedly increased FLI in the nucleus accumbens, frontal cortex and central amygdala.
Conclusions: These data provide further evidence for widespread roles for NmU and its receptors in the brain
First LIGO search for gravitational wave bursts from cosmic (super)strings
We report on a matched-filter search for gravitational wave bursts from
cosmic string cusps using LIGO data from the fourth science run (S4) which took
place in February and March 2005. No gravitational waves were detected in 14.9
days of data from times when all three LIGO detectors were operating. We
interpret the result in terms of a frequentist upper limit on the rate of
gravitational wave bursts and use the limits on the rate to constrain the
parameter space (string tension, reconnection probability, and loop sizes) of
cosmic string models.Comment: 11 pages, 3 figures. Replaced with version submitted to PR
Implications For The Origin Of GRB 051103 From LIGO Observations
We present the results of a LIGO search for gravitational waves (GWs)
associated with GRB 051103, a short-duration hard-spectrum gamma-ray burst
(GRB) whose electromagnetically determined sky position is coincident with the
spiral galaxy M81, which is 3.6 Mpc from Earth. Possible progenitors for
short-hard GRBs include compact object mergers and soft gamma repeater (SGR)
giant flares. A merger progenitor would produce a characteristic GW signal that
should be detectable at the distance of M81, while GW emission from an SGR is
not expected to be detectable at that distance. We found no evidence of a GW
signal associated with GRB 051103. Assuming weakly beamed gamma-ray emission
with a jet semi-angle of 30 deg we exclude a binary neutron star merger in M81
as the progenitor with a confidence of 98%. Neutron star-black hole mergers are
excluded with > 99% confidence. If the event occurred in M81 our findings
support the the hypothesis that GRB 051103 was due to an SGR giant flare,
making it the most distant extragalactic magnetar observed to date.Comment: 8 pages, 3 figures. For a repository of data used in the publication,
go to: https://dcc.ligo.org/cgi-bin/DocDB/ShowDocument?docid=15166 . Also see
the announcement for this paper on ligo.org at:
http://www.ligo.org/science/Publication-GRB051103/index.ph
Stacked Search for Gravitational Waves from the 2006 SGR 1900+14 Storm
We present the results of a LIGO search for short-duration gravitational
waves (GWs) associated with the 2006 March 29 SGR 1900+14 storm. A new search
method is used, "stacking'' the GW data around the times of individual
soft-gamma bursts in the storm to enhance sensitivity for models in which
multiple bursts are accompanied by GW emission. We assume that variation in the
time difference between burst electromagnetic emission and potential burst GW
emission is small relative to the GW signal duration, and we time-align GW
excess power time-frequency tilings containing individual burst triggers to
their corresponding electromagnetic emissions. We use two GW emission models in
our search: a fluence-weighted model and a flat (unweighted) model for the most
electromagnetically energetic bursts. We find no evidence of GWs associated
with either model. Model-dependent GW strain, isotropic GW emission energy
E_GW, and \gamma = E_GW / E_EM upper limits are estimated using a variety of
assumed waveforms. The stacking method allows us to set the most stringent
model-dependent limits on transient GW strain published to date. We find E_GW
upper limit estimates (at a nominal distance of 10 kpc) of between 2x10^45 erg
and 6x10^50 erg depending on waveform type. These limits are an order of
magnitude lower than upper limits published previously for this storm and
overlap with the range of electromagnetic energies emitted in SGR giant flares.Comment: 7 pages, 3 figure
Sensitivity to Gravitational Waves from Compact Binary Coalescences Achieved during LIGO's Fifth and Virgo's First Science Run
We summarize the sensitivity achieved by the LIGO and Virgo gravitational
wave detectors for compact binary coalescence (CBC) searches during LIGO's
fifth science run and Virgo's first science run. We present noise spectral
density curves for each of the four detectors that operated during these
science runs which are representative of the typical performance achieved by
the detectors for CBC searches. These spectra are intended for release to the
public as a summary of detector performance for CBC searches during these
science runs.Comment: 12 pages, 5 figure
Gravitational Waves From Known Pulsars: Results From The Initial Detector Era
We present the results of searches for gravitational waves from a large selection of pulsars using data from the most recent science runs (S6, VSR2 and VSR4) of the initial generation of interferometric gravitational wave detectors LIGO (Laser Interferometric Gravitational-wave Observatory) and Virgo. We do not see evidence for gravitational wave emission from any of the targeted sources but produce upper limits on the emission amplitude. We highlight the results from seven young pulsars with large spin-down luminosities. We reach within a factor of five of the canonical spin-down limit for all seven of these, whilst for the Crab and Vela pulsars we further surpass their spin-down limits. We present new or updated limits for 172 other pulsars (including both young and millisecond pulsars). Now that the detectors are undergoing major upgrades, and, for completeness, we bring together all of the most up-to-date results from all pulsars searched for during the operations of the first-generation LIGO, Virgo and GEO600 detectors. This gives a total of 195 pulsars including the most recent results described in this paper.United States National Science FoundationScience and Technology Facilities Council of the United KingdomMax-Planck-SocietyState of Niedersachsen/GermanyAustralian Research CouncilInternational Science Linkages program of the Commonwealth of AustraliaCouncil of Scientific and Industrial Research of IndiaIstituto Nazionale di Fisica Nucleare of ItalySpanish Ministerio de Economia y CompetitividadConselleria d'Economia Hisenda i Innovacio of the Govern de les Illes BalearsNetherlands Organisation for Scientific ResearchPolish Ministry of Science and Higher EducationFOCUS Programme of Foundation for Polish ScienceRoyal SocietyScottish Funding CouncilScottish Universities Physics AllianceNational Aeronautics and Space AdministrationOTKA of HungaryLyon Institute of Origins (LIO)National Research Foundation of KoreaIndustry CanadaProvince of Ontario through the Ministry of Economic Development and InnovationNational Science and Engineering Research Council CanadaCarnegie TrustLeverhulme TrustDavid and Lucile Packard FoundationResearch CorporationAlfred P. Sloan FoundationAstronom
Search for Gravitational Wave Bursts from Six Magnetars
Soft gamma repeaters (SGRs) and anomalous X-ray pulsars (AXPs) are thought to be magnetars: neutron stars powered by extreme magnetic fields. These rare objects are characterized by repeated and sometimes spectacular gamma-ray bursts. The burst mechanism might involve crustal fractures and excitation of non-radial modes which would emit gravitational waves (GWs). We present the results of a search for GW bursts from six galactic magnetars that is sensitive to neutron star f-modes, thought to be the most efficient GW emitting oscillatory modes in compact stars. One of them, SGR 0501+4516, is likely similar to 1 kpc from Earth, an order of magnitude closer than magnetars targeted in previous GW searches. A second, AXP 1E 1547.0-5408, gave a burst with an estimated isotropic energy >10(44) erg which is comparable to the giant flares. We find no evidence of GWs associated with a sample of 1279 electromagnetic triggers from six magnetars occurring between 2006 November and 2009 June, in GW data from the LIGO, Virgo, and GEO600 detectors. Our lowest model-dependent GW emission energy upper limits for band-and time-limited white noise bursts in the detector sensitive band, and for f-mode ringdowns (at 1090 Hz), are 3.0 x 10(44)d(1)(2) erg and 1.4 x 10(47)d(1)(2) erg, respectively, where d(1) = d(0501)/1 kpc and d(0501) is the distance to SGR 0501+4516. These limits on GW emission from f-modes are an order of magnitude lower than any previous, and approach the range of electromagnetic energies seen in SGR giant flares for the first time.United States National Science FoundationScience and Technology Facilities Council of the United KingdomMax-Planck-SocietyState of Niedersachsen/GermanyItalian Istituto Nazionale di Fisica NucleareFrench Centre National de la Recherche ScientifiqueAustralian Research CouncilCouncil of Scientific and Industrial Research of IndiaIstituto Nazionale di Fisica Nucleare of ItalySpanish Ministerio de Educacion y CienciaConselleria d'Economia Hisenda i Innovacio of the Govern de les Illes BalearsFoundation for Fundamental Research on Matter supported by the Netherlands Organisation for Scientific ResearchPolish Ministry of Science and Higher EducationFoundation for Polish ScienceRoyal SocietyScottish Funding CouncilScottish Universities Physics AllianceNational Aeronautics and Space Administration NNH07ZDA001-GLASTCarnegie TrustLeverhulme TrustDavid and Lucile Packard FoundationResearch CorporationAlfred P. Sloan FoundationRussian Space AgencyRFBR 09-02-00166aIPN JPL Y503559 (Odyssey), NASA NNG06GH00G, NASA NNX07AM42G, NASA NNX08AC89G (INTEGRAL), NASA NNG06GI896, NASA NNX07AJ65G, NASA NNX08AN23G (Swift), NASA NNX07AR71G (MESSENGER), NASA NNX06AI36G, NASA NNX08AB84G, NASA NNX08AZ85G (Suzaku), NASA NNX09AU03G (Fermi)Astronom
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